A Study to Assess the Efficacy and Safety of the VEGFR-FGFR Inhibitor, Lucitanib, Given to Patients With Advanced/Metastatic Lung Cancer and FGF, VEGF, or PDGF Related Genetic Alterations

NCT ID: NCT02109016

Last Updated: 2019-07-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-09-30

Brief Summary

The purpose of this study is to determine whether lucitanib is safe and effective in the treatment of patients with advanced/metastatic lung cancer and fibroblast growth factor (FGF), vascular endothelial growth factor receptor (VEGF), or platelet derived growth factor (PDGF) related genetic alterations.

Detailed Description

Lucitanib is an oral inhibitor of the tyrosine kinase activity of FGFR 1-3, VEGFR 1-3, and PDGFR α/β. Lucitanib has demonstrated potent anti-tumor and anti-angiogenic activity in vitro proliferation assays and in vivo using human tumor xenograft models, with a trend for stronger efficacy in those with genomic aberrancies of FGF or PDGF. Abnormalities in the FGF, VEGF, and PDGF-related genes are observed across lung cancer histologies.

The first in human trial of lucitanib demonstrated that daily lucitanib is clinically active in patients with advanced solid tumors. Specifically, patients with FGFR1-amplification appeared to derive particular benefit from lucitanib.

Based on these results, this study is designed to explore the safety and anti-tumor activity of daily lucitanib in lung cancer patients with FGF, VEGF, and PDGF genetic alterations.

Conditions

Non-Small Cell Lung Cancer; Squamous Non-Small Cell Lung Cancer; NSCLC; Small Cell Lung Cancer; SCLC; Lung Cancer; Advanced Lung Cancer; Metastatic Lung Cancer; Stage IV Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lucitanib

Lucitanib given orally once daily on a continuous schedule. Starting dose is 10 mg/day.

Group Type: EXPERIMENTAL

Lucitanib

Intervention Type: DRUG

Lucitanib given orally to all patients, once daily (q.d.), on a continuous schedule over 28-day cycles, in fasting conditions (at least 2 hours prior to and 2 hours after any meal), until progressive disease or unacceptable toxicity.

Starting dose is 10 mg/day and can be reduced in 2.5 mg decrements to 5 mg/day based on individual tolerability.

Interventions

Lucitanib

Lucitanib given orally to all patients, once daily (q.d.), on a continuous schedule over 28-day cycles, in fasting conditions (at least 2 hours prior to and 2 hours after any meal), until progressive disease or unacceptable toxicity.

Starting dose is 10 mg/day and can be reduced in 2.5 mg decrements to 5 mg/day based on individual tolerability.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed advanced/metastatic SCLC or NSCLC
• Any of the following tumor tissue based genetic alterations: FGFR1, FGFR2, FGFR3, VEGFA, or PDGFRα amplification; Any FGFR1, FGFR2, or FGFR3 gene fusion; FGFR1, FGFR2, or FGFR3 activating mutation
• Availability of tumor tissue sample suitable for the central confirmation of the genetic alteration and exploratory analyses
• Eastern Cooperative Oncology Group (ECOG) of 0 or 1
• Measurable disease per RECIST 1.1
• Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting

Exclusion Criteria

• Tumors that are invading a major vessel; NSCLC tumors abutting to a major vessel
• Uncontrolled hypertension, defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg with optimized anti-hypertensive therapy
• Uncontrolled hypothyroidism defined as serum thyroid stimulating hormone (TSH) higher than 5 mIU/mL while receiving appropriate thyroid hormone therapy
• Symptomatic and/or untreated central nervous system metastases
• Presence of another active cancer
• Ongoing adverse events from surgery or prior anti-cancer therapies, including radiation, targeted, or cytotoxic therapies
• Pregnant or breastfeeding women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California, Los Angeles

Los Angeles, California, United States

University of Colorado

Aurora, Colorado, United States

Georgetown University

Washington D.C., District of Columbia, United States

Emory University

Atlanta, Georgia, United States

Associates in Oncology and Hematology

Rockville, Maryland, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

CHU Caen, Hôpital de la Côte de Nacre

Caen, , France

CHRU Lille, Hôpital Albert Calmette

Lille, , France

Hôpital Nord

Marseille, , France

Institut Gustave-Roussy

Villejuif, , France

Universität Duisburg-Essen

Essen, , Germany

Hospital Grosshansdorf

Großhansdorf, , Germany

Pius Hospital Oldenburg

Oldenburg, , Germany

Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

AOU San Luigi Gonzaga

Orbassano, , Italy

Ospedale S. Maria della Misericordia

Perugia, , Italy

Hospital Universitari Vall d'Hebrón

Barcelona, Catalonia, Spain

Countries

United States; France; Germany; Italy; Spain

References

Liao M, Zhou J, Wride K, Lepley D, Cameron T, Sale M, Xiao J. Population Pharmacokinetic Modeling of Lucitanib in Patients with Advanced Cancer. Eur J Drug Metab Pharmacokinet. 2022 Sep;47(5):711-723. doi: 10.1007/s13318-022-00773-w. Epub 2022 Jul 18.

Reference Type: DERIVED

PMID: 35844029 (View on PubMed)

Other Identifiers

E-3810-II-02

Identifier Type: -

Identifier Source: org_study_id